We have developed a new method for sampling "loop of Henle fluid" during antidiuresis in regular clearance experiments in the dog. We propose to apply this to the problem of drug distribution within the kidney with particular attention given to the concentrations of drugs achieved in the urine, the parenchyma of the papilla, and the loop of Henle during antidiuresis. The data will provide insight into the mechanisms of drug excretion, and is particularly relevant to problems of chemotherapy and to the pathogenesis of nephrotoxic reactions. Drugs responsible for analgesic nephritis will receive special attention. In the preliminary experiments we will study a series of sulfonamides known to have a wide range of clearance. Uric acid and the minor electrolytes will also be examined. Changes in acid-base balance warrant selective study in relation to drugs whose excretion is pH dependent.